5f8y

Structural highlights

Function

LEC_CREGR Galactose-binding lectin (PubMed:23886951, PubMed:27010847, PubMed:9568372, PubMed:28636877). Binds both alpha and beta anomer of galactose (Gal), but has a stronger interaction with the glycans having alpha Gal at the non-reducing end and binds beta Gal weakly only in highly branched glycans. Has high affinity to Galalpha1-4Galbeta1-4GlcNAc (PubMed:28636877). Binds N-acetyl-2-deoxy-2-amino-galactose (2-deoxy-GalNAc) (PubMed:23886951, PubMed:9568372). Binds N-acetylgalactosamine (GalNAc) (PubMed:26439416). Binds porcine stomach mucin (PSM) with high affinity (PubMed:26439416, PubMed:30486373). Binds galactosamine (PubMed:27010847). Binds laminin, bovine submaxillary mucin (BSM), fibronectin, type I collagen and gelatin with a decreasing affinity, respectively (Ref.3). Has hemagglutinating activity towards human type A erythrocytes (PubMed:9568372, PubMed:26439416, Ref.3). Hemagglutinates also human type 0, B and AB erythrocytes as well as rabbit and mouse erythrocytes (PubMed:9568372). Agglutinates both Gram-positive and Gram-negative bacteria including B.subtilis ATCC 6633, S.aureus ATCC 21027 and E.coli 3254, respectively. No agglutination activity towards Gram-positive S.amurskyense CMM 3673. Has bacteriostatic activity on S.amurskyense CMM 3673, B.subtilis ATCC 6633, S.aureus ATCC 21027 and E.coli 3254. However, has no agglutination nor bacteriostatic activity on Gram-negative C.scophthalmum CIP 104199 or A.troitsensis KMM 3674 (PubMed:23886951). Inhibits growth of fungi from the genera Aspergillus, Penicillium, Trichoderma and st. Mycelia. Inhibits germination of spores and hyphal growth of them (PubMed:25482060). Has dose-dependent cytotoxic effect on the human globotriaosylceramide (Gb3)-expressing Burkitt's lymphoma (Raji) cell line. Binds to Gb3 in these cells leading to activation of caspase-9/3 and PARP (PubMed:28636877). Has dose-dependent cytotoxic effect on the Gb3-expressing human MCF-7 breast cancer cell line (PubMed:27010847). No cytotoxic effect on myelogenous leukemia K562 cell line, which does not express Gb3 (PubMed:28636877). Activates immune responses in mice and increases cytokine production of TNF-alpha, IL-6 and MCP-1 in the serum and the peritoneal lavage of mice. Induces TNF-alpha and IL-6 secretion in mouse RAW264.7 macrophages, mouse bone marrow-derived macrophages, human THP-1 macrophages, human peripheral blood mononuclear cells (PBMCs) and human blood monocyte-derived macrophages. TNF-alpha production in macrophages could not be inhibited by GalNAc, GalN or Gal, indicating that induced cytokine production is separate from its sugar binding activity. Increases intracellular reactive oxygen species levels, expression and phosphorylation of protein kinases PKC alpha/delta, expression of COX-2 and NF-kappaB, and activates the MAPK pathway by increasing the phosphorylation of ERK1/2, JNK1/2 and p38 in mouse RAW264.7 macrophages. Induces endotoxin tolerance in lipopolysaccharide(LPS)-activated macrophages by down-regulating IRAK2 expression, reducing JNK1/2 phosphorylation and NF-kappaB activation. Can slightly increase the bactericidal activity of RAW264.7 macrophages (PubMed:28740170). Has DNA-binding activity (PubMed:27010847). Recognizes pathogen-associated molecular patterns (PAMPs) and binds to LPS from E.coli, but has only little binding to beta-1,3-glucan from E.gracilis and peptidoglycan from S.aureus. Activates secretion of TNF-alpha and IFN-gamma by the human peripheral blood cells (HPBCs) (PubMed:31905927). May be involved in innate immunity acting as an antibacterial and antifungal agent involved in the recognition and clearance of pathogens (PubMed:23886951, PubMed:25482060, PubMed:31905927).^{[1] [2] [3] [4] [5] [6] [7] [8] [9] [10]}

References

1. ↑ Kovalchuk SN, Chikalovets IV, Chernikov OV, Molchanova VI, Li W, Rasskazov VA, Lukyanov PA. cDNA cloning and structural characterization of a lectin from the mussel Crenomytilus grayanus with a unique amino acid sequence and antibacterial activity. Fish Shellfish Immunol. 2013 Oct;35(4):1320-4. PMID:23886951 doi:10.1016/j.fsi.2013.07.011
2. ↑ Chikalovets IV, Chernikov OV, Pivkin MV, Molchanova VI, Litovchenko AP, Li W, Lukyanov PA. A lectin with antifungal activity from the mussel Crenomytilus grayanus. Fish Shellfish Immunol. 2015 Feb;42(2):503-7. PMID:25482060 doi:10.1016/j.fsi.2014.11.036
3. ↑ Kovalchuk SN, Golotin VA, Balabanova LA, Buinovskaya NS, Likhatskaya GN, Rasskazov VA. Carbohydrate-binding motifs in a novel type lectin from the sea mussel Crenomytilus grayanus: Homology modeling study and site-specific mutagenesis. Fish Shellfish Immunol. 2015 Nov;47(1):565-71. PMID:26439416 doi:10.1016/j.fsi.2015.09.045
4. ↑ Liao JH, Chien CT, Wu HY, Huang KF, Wang I, Ho MR, Tu IF, Lee IM, Li W, Shih YL, Wu CY, Lukyanov PA, Hsu ST, Wu SH. A Multivalent Marine Lectin from Crenomytilus grayanus Possesses Anti-cancer Activity through Recognizing Globotriose Gb3. J Am Chem Soc. 2016 Apr 13;138(14):4787-95. doi: 10.1021/jacs.6b00111. Epub 2016 , Apr 1. PMID:27010847 doi:http://dx.doi.org/10.1021/jacs.6b00111
5. ↑ Chernikov O, Kuzmich A, Chikalovets I, Molchanova V, Hua KF. Lectin CGL from the sea mussel Crenomytilus grayanus induces Burkitt's lymphoma cells death via interaction with surface glycan. Int J Biol Macromol. 2017 Nov;104(Pt A):508-514. PMID:28636877 doi:10.1016/j.ijbiomac.2017.06.074
6. ↑ Chernikov OV, Wong WT, Li LH, Chikalovets IV, Molchanova VI, Wu SH, Liao JH, Hua KF. A GalNAc/Gal-specific lectin from the sea mussel Crenomytilus grayanus modulates immune response in macrophages and in mice. Sci Rep. 2017 Jul 24;7(1):6315. PMID:28740170 doi:10.1038/s41598-017-06647-5
7. ↑ Kovalchuk SN, Buinovskaya NS, Likhatskaya GN, Rasskazov VA, Son OM, Tekutyeva LA, Balabanova LA. Mutagenesis Studies and Structure-function Relationships for GalNAc/Gal-Specific Lectin from the Sea Mussel Crenomytilus grayanus. Mar Drugs. 2018 Nov 27;16(12):471. PMID:30486373 doi:10.3390/md16120471
8. ↑ Chikalovets I, Filshtein A, Molchanova V, Mizgina T, Lukyanov P, Nedashkovskaya O, Hua KF, Chernikov O. Activity Dependence of a Novel Lectin Family on Structure and Carbohydrate-Binding Properties. Molecules. 2019 Dec 30;25(1):150. PMID:31905927 doi:10.3390/molecules25010150
9. ↑ Belogortseva NI, Molchanova VI, Kurika AV, Skobun AS, Glazkova VE. Isolation and characterization of new GalNAc/Gal-specific lectin from the sea mussel Crenomytilus grayanus. Comp Biochem Physiol C Pharmacol Toxicol Endocrinol. 1998 Jan;119(1):45-50. PMID:9568372 doi:10.1016/s0742-8413(97)00180-1
10. ↑ Chikalovets IV, Chernikov OV, Pivkin MV, Molchanova VI, Litovchenko AP, Li W, Lukyanov PA. A lectin with antifungal activity from the mussel Crenomytilus grayanus. Fish Shellfish Immunol. 2015 Feb;42(2):503-7. PMID:25482060 doi:10.1016/j.fsi.2014.11.036